Patients with low serum 25(OH)D appeared to benefit in meta-analysis

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Vitamin D supplementation was associated with a 50% reduction in the risk of an asthma attack resulting in an emergency department visit or hospitalization, according to a meta-analysis.

Note that while the new data raise the possibility that those with the lowest vitamin D levels may benefit the most, this has not been shown definitively.

Vitamin D supplementation was associated with a 50% reduction in the risk of experiencing an asthma attack resulting in a emergency department visit or hospitalization, according to a meta-analysis using patient-level data.

With 955 asthma patients participating in seven randomized controlled trials, the analysis also showed oral vitamin D use to be associated with a 30% reduction in the rate of asthma attacks requiring treatment with steroid pills or injections.

The effect appeared to reach statistical significance in patients with low baseline vitamin D levels (less than 25 nmol/L), but not in patients with higher baseline levels, said Adrian Martineau, PhD, of the Barts and The London School of Medicine and Dentistry's Blizard Institute in London.

"This fits with our broad understanding that vitamin D supplementation is likely to confer the greatest benefit to those who have the lowest vitamin D levels to begin with," Martineau told MedPage Today, adding that the effects of vitamin D in patients with higher baseline levels were borderline significant.

"It may well be that this group of patients may also benefit, albeit more modestly," he added. "We hope to incorporate more data from on-going trials in the years ahead, which will give us greater statistical power to look at effects in these two sub-groups."

Martineau said the study is the first individual participant data (IPD) meta-analysis to examine the potential role of vitamin D supplementation on asthma exacerbation risk.

In a recent Cochrane review, the researchers concluded that vitamin D supplementation was associated with a 37% reduction in the risk of asthma exacerbations requiring systemic corticosteroids. But IPD was not available in the studies included in that analysis.

"Uniquely, access to individual participant data allowed us to conduct sub-group analyses to investigate whether vitamin D 'works' better in some people than others," Martineau noted in an email exchange. "Aggregate data meta-analysis (the conventional approach to meta-analysis – which we used in our recent Cochrane review on this subject) can't do this."

Of 483 studies identified by Martineau and colleagues, eight were eligible randomized controlled trials, but just seven had individual participant data.

Mixed-effects regression models were used to determine the pooled intervention effect with a 95% confidence interval, and subgroup analyses were conducted to determine whether factors such as baseline 25(OH)D level, age, ethnic or racial origin, BMI, vitamin D dosing regimen, use of inhaled corticosteroids or end-of-study 25(OH)D level affected the association.

Just 3% of patients receiving vitamin D had at least one exacerbation requiring an emergency department visit or hospitalization, compared to 6% of placebo-treated patients.

There were no significant differences between the vitamin D and placebo groups in the proportion of participants with at least one exacerbation or time to first exacerbation.

Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0.33, 95% CI 0.11–0.98; P=0.046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0.77, 95% CI 0.58–1.03; P=0.08; 764 participants in six studies; moderate-quality evidence; P=0.25 for interaction).

"High quality evidence from randomized placebo-controlled trials indicates that vitamin D supplementation can reduce risk of asthma attacks," Martineau noted. "Our new article raises the possibility that those with the lowest vitamin D levels may benefit the most, but we have not yet shown this definitively."

He added that he believes there is now a strong case to be made for testing vitamin D levels in patients with asthma who experience exacerbations, and for giving a daily oral vitamin D3 to those who are found to be vitamin D deficient.

But in an editorial published with the study, respiratory medicine specialists Richard Beasley and Mark Weatherall of the Medical Research Institute of New Zealand in Wellington noted that methodological limitations, including insufficient power to determine whether the risk reductions were significantly different in patients with low and higher 25(OH)D, limit the interpretation of the findings.

"Certainly there is a case to answer and definitive well powered randomized placebo controlled trials need to be done as a priority because the magnitude of the reduction in risk of severe exacerbations with vitamin D reported in this meta-analysis is substantial," they wrote.

Beasley and Weatherall added that in addition to determining the efficacy of vitamin D supplementation in asthma, future randomized controlled trials must also be sufficiently powered and designed to determine whether vitamin D level or other characteristics impact response.

"If true then the specific characteristic of the patient would represent a treatable trait and allow a precision medical approach to be implemented," they wrote.

Funding for this study was provided by the Health Technology Assessment Program, National Institute for Health Research.

The researchers declared no relevant relationships with industry related to this study.

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